Chemical aspects of the major oxidative metabolic pathways of the beta-adrenergic blockers propranolol, metoprolol and bufuralol will be investigated. Structural and mechanistic chemical and stereochemical aspects of these processes will be examined. The major pathways to be explored are aromatic hydroxylation, including multiple hydroxylations, and the multistep N-dealkylation processes for propranolol; the alpha- hydroxylation (benzylic), O-demethylation and subsequent oxidation for metoprolol; and the benzylic hydroxylation of bufuralol. Some potential metabolites will be synthesized, and identification will be accomplished using the techniques of stable isotope labeling, hplc separation and GC-mass spectral determination. Stereochemical aspects of these pathways will be studied using the individual enantiomers and pseudoracemates of propranolol, racemic propranolol, enantiomers and pseudoracemates of metoprolol and of bufuralol. Experiments will be done in vitro (fractions from rat homogenates and human liver) and in vivo (in rats). Limited experiments in human subjects are proposed.